What Is Leuprorelin Acetate (Eligard)? FDA Approval, Licensing in Turkey, and Reimbursement Status

• FDA-Approved: Yes (First approval date: January 25, 2002)
• Product Name: Eligard
• Active Ingredient Name: Leuprorelin acetate
• Method of Administration: Subcutaneous (SC) injection
• Class: LHRH Agonist (Luteinizing Hormone-Releasing Hormone Agonist)
• Category: Hormonal Agent
• Distribution in Turkey: Recordati
• Approved Cancers:
  • Hormone-sensitive metastatic or locally advanced prostate cancer is treated with this drug.

What Is Eligard?

Eligard, containing the active ingredient leuprorelin acetate, is an LHRH agonist used to treat prostate cancer. It lowers testosterone levels by suppressing the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Through this mechanism, it slows or stops the growth of hormone-sensitive tumors.

What Is an LHRH Agonist?

LHRH agonists stimulate the pituitary gland, initially causing a temporary increase in LH and FSH. With prolonged use, however, the pituitary gland becomes desensitized, and LH and FSH production is suppressed. As a result, testosterone falls to castrate levels.

How Does It Work?

• It Initiates LH and FSH Secretion:
  • During the first few days of treatment, the pituitary gland is stimulated, temporarily increasing LH and FSH levels.
  • This may cause a temporary rise in testosterone levels (tumor flare).
• LH and FSH Are Suppressed:
  • Over time, the pituitary gland becomes desensitized to LHRH, and LH-FSH production is suppressed.
  • This reduces testosterone production and inhibits the growth of prostate cancer cells.
• Testosterone Falls to Castrate Levels:
  • Plasma testosterone levels generally fall to castrate levels within 2-4 weeks.
  • This slows or stops disease progression in hormone-dependent tumors.

FDA (United States Food and Drug Administration) Approval History

• January 25, 2002:
  • It received FDA approval for the treatment of patients with advanced prostate cancer.
• October 12, 2004:
  • The FDA approved the 22.5 mg formulation of Eligard as an injection administered every three months.
• June 28, 2006:
  • The FDA approved the 30 mg formulation for administration every four months.
• December 24, 2008:
  • Eligard received FDA approval as neoadjuvant therapy combined with radiotherapy in patients with early-stage prostate cancer.
• November 15, 2011:
  • It was approved by the FDA to treat hormone-sensitive metastatic prostate cancer.

Licensing in Turkey

The conditions for which Eligard is licensed in Turkey / its therapeutic indications are listed as follows:

Therapeutic Indications

• For the treatment of advanced prostate cancer suitable for hormonal intervention 
• It is indicated in combination with radiotherapy for high-risk localized and locally advanced prostate cancer suitable for hormonal intervention.

Is Eligard Reimbursed?

The treatment situations in which Eligard is covered by the Social Security Institution (SGK) are as follows:

• For the treatment of advanced prostate cancer suitable for hormonal intervention 
• It is covered by SGK in combination with radiotherapy for high-risk localized and locally advanced prostate cancer suitable for hormonal intervention.

Price: As of August 2025, the pharmacy retail price of ELIGARD 22.5 mg and 45mg powder for s.c. solution for injection in a syringe with a solvent syringe was 7283.94 ₺ /14,423.51 ₺

What Is Eligard's Status on the List of Off-Label Drugs That Can Be Used Without Additional TİTCK Approval?

• Stage IV Breast Cancer: Suitable for use in premenopausal breast cancer.
• Early-Stage Breast Cancer: Suitable for use in premenopausal breast cancer.
• Metastatic Adenoid Cystic Carcinoma: Suitable for use in the 2nd and subsequent lines of treatment in androgen receptor-positive patients with metastatic disease.

Resistance Mechanisms

Eligard acts as a luteinizing hormone-releasing hormone (LHRH) agonist and is used to treat prostate cancer by suppressing testosterone levels. However, some patients may develop drug resistance over time. The mechanisms of resistance can be summarized as follows:

• Androgen Receptor (AR) Overexpression:
  • Prostate cancer cells may overexpress androgen receptors (AR), allowing them to continue growing even at low testosterone levels.
• Loss of Androgen Dependence:
  • Some cancer cells continue growing by activating androgen-independent proliferation pathways, which may lead to the development of castration-resistant prostate cancer (CRPC) .
• Activation of Alternative Signaling Pathways:
  • Activation of signaling pathways that support cell growth, such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR, may cause cancer cells to become resistant to LHRH agonists.
• Testosterone Synthesis from Extratumoral Sources:
  • Although testosterone production is suppressed in the testes, the adrenal glands and tumor microenvironment may provide alternative sources of androgens.
• Androgen Receptor Mutations and Variants:
  • Certain AR mutations may reduce drug effectiveness, allowing the cancer to continue growing.
• Glucocorticoid Receptor Activation:
  • Glucocorticoid receptor activation may sustain cancer cell growth by taking over the role of the androgen receptor.

These mechanisms explain resistance to LHRH agonists and highlight the need for alternative treatment approaches (antiandrogens, second-generation androgen receptor antagonists, etc.).

Pharmacokinetic Properties

• Absorption
  • Eligard is not absorbed orally.
  • After subcutaneous (SC) injection, approximately 90% of the dose enters the systemic circulation.
  • Its bioavailability is very high, and it is absorbed rapidly after injection.
• Distribution
  • The distribution of leuprorelin has not been fully characterized. 
  • It is released slowly over 28 days.
  • Peak plasma concentration (Cmax) is reached 10-15 days after injection.
  • Plasma protein binding ranges from 45-50%.
• Metabolism
  • Leuprorelin is metabolized mainly through hydrolysis of its C-terminal amino acids.
  • It is largely excreted unchanged in urine (> 90%).
  • The elimination half-life is normally 3-4 hours.
  • The half-life may be prolonged in patients with impaired kidney function.
• Dosage Range
  • A 22.5 mg SC injection may be administered every 3 months.
  • Alternatively, a 45 mg SC injection may be administered every 6 months.

Treatment duration and the dosing interval should be determined according to the patient's clinical condition.

Drug Interactions

Based on available data, there are no well-defined drug interactions associated with Eligard (leuprorelin).

Precautions

• Risk of Tumor Flare at the Start of Treatment:
  • At the start of leuprorelin treatment, there may be a temporary increase in the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
  • This may cause tumor flare in some patients.
  • This risk is higher particularly in patients with ureteral obstruction, spinal cord compression, or painful bone metastases.
  • To prevent tumor flare in these patients, at least 1 week before starting leuprolide, antiandrogen treatment (such as bicalutamide) should be started.
• Decreased Testosterone Levels:
  • Testosterone falls to castrate levels 2-4 weeks after leuprolide treatment begins.
  • Regular monitoring of testosterone levels is therefore recommended.
• Cautious Use in Patients with Renal Impairment:
  • Leuprorelin should be used cautiously in patients with impaired kidney function.
  • The elimination half-life may be prolonged in patients with renal impairment.
• Risk of Hot Flashes:
  • Patients should be informed of the risk of hot flashes.
  • Clonidine (0.1-0.2 mg PO daily), megestrol acetate (20 mg PO twice daily), or soy tablets (1 tablet PO three times daily) may be considered for prevention and/or treatment.

Adverse Effects

• Hot flashes, impotence, and gynecomastia:
  • Leuprorelin use may cause hot flashes, decreased sexual desire (loss of libido), erectile dysfunction (impotence), and gynecomastia.
  • Loss of libido is generally less common.
• Tumor Flare:
  • It may occur in 20% of patients during the first 2 weeks of treatment.
  • Symptoms: Increased bone pain, urinary retention (difficulty urinating), and back pain associated with spinal cord compression
  • Prevention: Pretreatment with antiandrogens such as flutamide, bicalutamide, or nilutamide may be given before treatment.
• Injection-Site Discomfort:
  • Leuprorelin may cause pain, swelling, and tenderness at the injection site.
• Increased Serum Cholesterol Levels:
  • LDL and total cholesterol levels may increase.
  • Regular lipid monitoring is recommended in patients with cardiovascular risk.
• Nausea and Vomiting:
  • Nausea and vomiting may occur rarely.
• Hypersensitivity Reactions:
  • Hypersensitivity reactions such as itching, rash, or anaphylactic reactions have been reported.
• Peripheral Edema:
  • Swelling of the legs and hands may develop due to sodium retention.
• Muscle Weakness (Asthenia):
  • Fatigue, lack of energy, and muscle weakness may occur.